1. Field of the Invention
The present invention relates to a composition or a method for preventing treating, improving and/or ameliorating a disease associated with β-amyloid in brain which is at least one selected from dementia, ameliorating memory impairment and memory, by using a composition including arylnaphthalene lignan derivative, in particular, Justicidin A, 5-methoxyjusticidin A, Chinensinaphthol and/or a pharmaceutically-acceptable salt thereof.
2. Description of the Related Art
Generally, dementia is a symptom showing remarkably decreased brain functions such as the abilities of memory, thinking, understanding, calculating, learning, language, and judgment where the brain normal cell is damaged due to various reasons.
In particular, Alzheimer's disease is a most important disease of senile dementia, and is mainly caused by the accumulation of β-amyloid in brain and its neurotoxicity (Probst A. et al., Brain Pathol., 1:229-239, 1991). It has been reported that β-amyloid makes the protein plaque in brain, thereby causing the occurrence of Alzheimer's disease (Breimer L H, et al. Nature, 326: 749-750, 1987).
β-amyloid is formed by the sequential interaction of amyloid precursor protein (APP) with β-secretase (BACE1) and gamma-secretase (Vassa and Citron, Neuron 27, 419-422, 2000). β-amyloid is largely classified into two types of Aβ40 of 40 amino acids and Aβ42 of 42 amino acids. β-amyloid is mainly Aβ40, but relatively small amounts of Aβ42 makes the plaque formation easier and thus is considered as a factor causing the disease (Selkoe, Science 298: 789-891, 2002).
The cleavage of APP is caused by two different enzymes of alpha-secretase and beta-secretase, which have opposite control activities in the formation of beta-amyloid. Beta-secretase acts largely on the formation of Aβ42 and APP-β, while alpha-secretase results in the formation of APP-α having a neuron protecting activity and reduces the formation of beta-amyloid relatively. Unlike the beta-secretase, organic compounds with low molecular weight which activate the alpha-secretase have not been researched as yet, and the studies on the identification and mechanism for the alpha-secretase are on-going at a molecular level (Kuhn et al, EMBO Journal, 2010, 29, 3020). Accordingly, the alpha-secretase draws an attention as a new molecular target for developing a drug treating Alzheimer's disease.
The commercially available representative drugs for treating dementia are tacrine (Cognex, 1994) and donepezil (Aricept, 1996) used after U.S. FDA approval. The mechanism of drugs to prevent and treat the dementia has been known to increase the concentration of the neurotransmitter acetylcholine by inhibiting the activity of acetylcholinesterase AChE degrading the acetylcholine. However, tacrine has serious hepatotoxicity. Donepezil does not have hepatotoxicity, but causes various side-effects such as nausea, anorexia, diarrhea, and etc. by stimulating the parasympathetic nerve.
Therefore, a new drug for treating dementia which can treat the causes of disease without the side-effects is still needed and has been studied actively. As a part of the studies, there are efforts to develop continuously a drug for inhibiting the β-amyloid formation.
Justicidin A having arylnaphthalene lignan structure was separated as an active ingredient of fish poison of Justicia hayatai for the first time (Munakata et al, Tetrahedron Letters, 1965, (47), 4167). Justicidin A was subsequently separated from various sources and showed different activities. However, Justicidin A has not been reported to have an effect for preventing and/or treating dementia, and improving the memory function.
5-methoxyjusticidin A is a derivative of arylnaphthalene lignan. It was reported in Protium unifoliolatum for the first time (Sian et al, J. Nat. Prod. 1998, 61, 796), but the efficacy was not reported at all.
Chinensinaphthol, an arylnaphthalene lignan derivative was reported in Justicia procumbens (Chen et al, J. Nat. Prod. 1996, 59, 1149), but has not been reported to have any efficacy on the memory, brain disorder, or dementia.
Particularly, it has not been reported or known nearly that hundreds of arylnaphthalene lignan or derivatives thereof including Justicidin A, 5-methoxyJusticidin A, and Chinensinaphthol have an effect on the memory, brain disorder, or dementia.